Drug Interactions between etravirine and Voquezna Triple Pak

GENERALLY AVOID: Coadministration with etravirine may decrease the plasma concentrations of clarithromycin and increase concentrations of the active metabolite, 14-hydroxy-clarithromycin. The mechanism is etravirine induction of CYP450 3A4, the isoenzyme that metabolizes clarithromycin to 14-hydroxy-clarithromycin. In 15 study subjects administered clarithromycin 500 mg twice a day with etravirine, clarithromycin peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 34%, 39% and 53%, respectively, while Cmax, AUC and Cmin of 14-hydroxy-clarithromycin increased by 33%, 21% and 5%, respectively. Etravirine Cmax, AUC, and Cmin also increased by over 40% each due to inhibition of its CYP450 3A4 metabolism by clarithromycin.

MANAGEMENT: Because 14-hydroxy-clarithromycin has demonstrated reduced activity relative to the parent drug against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered during coadministration of clarithromycin with etravirine. Therefore, alternatives to clarithromycin (e.g., azithromycin) should be considered for the treatment of MAC in patients receiving etravirine.

GENERALLY AVOID: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with moderate CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 50%. Reduced efficacy of vonoprazan may occur.

MANAGEMENT: According to the manufacturer, concomitant use of vonoprazan with moderate CYP450 3A4 inducers should be avoided.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.